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Cited by 19Metabolomics and Mass Spectrometry StudiesSphingolipid Metabolism and SignalingMass Spectrometry Techniques and Applications

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Multiplatform Lipid Analysis of the Brain of Aging Mice by Mass Spectrometry

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Panda, Punyatoya, Ferreira, Christina R., Cooper, Bruce R., Schaser, Allison J., Aryal, Uma K.·2025·Journal of Proteome Research
DOI 10.1021/acs.jproteome.4c00688

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Abstract

Abstract Lipids are an integral part of brain structure and function and represent about 50% of the dry weight of the brain. Despite their importance, the complexity and variations in the abundance of brain lipids due to aging remain poorly understood. For maximum coverage and multi-platform validation, we applied three complementary mass spectrometry-based analytical approaches: multiple reaction monitoring (MRM) profiling, untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS), and desorption electrospray ionization-MS imaging (DESI-MSI). We used three different age groups of mice, namely adult (3-4 months), middle-aged (10 months) and old (19-21 months). Phospholipids including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) showed higher abundance, while phosphatidylinositols (PI) and phosphatidylserines (PS) generally showed lower abundance in the brains of old mice compared to adults or middle-aged mice. Polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), as well as hexosylceramides (HexCer), sulfated hexosylceramides (SHexCer) and sphingomyelins (SM) were among the most abundant lipid species in the brains of old mice. DESI-MSI showed variations in the spatial distribution of many of the lipids confirmed by MRM and LC-MS/MS profiling. Interrogation of lipidomic data with recent proteomics data obtained from the same tissues revealed changes in the abundance and phosphorylation levels of several proteins potentially linked to ceramide (Cer), hexosylceramide (HexCer), fatty acids (FA), phosphatidylinositol (PI), sphingomyelin (SM) and sulfatides (SHexCer) metabolism and correlated well with the multiplatform lipid surveillance. Our findings offer insight into age-dependent changes in brain lipid profiles and their potential contribution to age-related cognitive decline.

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Metadata

Authors
Panda, P., Ferreira, C. R., Cooper, B. R., Schaser, A. J., & Aryal, U. K.
Affiliations
Purdue University West Lafayette (US)
Corresponding author
  • Schaser, Allison J.
  • Aryal, Uma K.
ORCID
Venue
Journal of Proteome Research
Publisher
American Chemical Society (ACS)
Published
2025-02-08
Volume
24
Issue
3
Pages
1077-1091
ISSN
  • 1535-3893 (ISSN-L)
  • 1535-3907
DOI
10.1021/acs.jproteome.4c00688
OpenAlex
W4407267889
Cited by
19
References
5
Citations by year
2026: 14 · 2025: 5
FWCI
5.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Proteome Research (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Indiana Clinical and Translational Sciences Institute
  • Purdue University
  • Ralph W. and Grace M. Showalter Research Trust Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
Keywords
brain lipids, brain aging, phospholipids, phosphatidylcholine, phosphatidylinositol, phosphatidylserine, polyunsaturated fatty acids, docosahexaenoic acid, arachidonic acid, sphingomyelin, hexosylceramide, lipid spatial distribution, age-related cognitive decline, protein-lipid interactions, mouse brain
MeSH terms
Lipidomics, Aging, Animals, Brain, Brain Chemistry, Chromatography, Liquid, Lipids, Male, Mice, Inbred C57BL, Phosphatidylethanolamines, Phospholipids, Spectrometry, Mass, Electrospray Ionization, Lipid Metabolism, Mice, Tandem Mass Spectrometry

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CoChat. (2026). Citation check: Multiplatform Lipid Analysis of the Brain of Aging Mice by Mass Spectrometry. https://app.cochat.ai/papers/10.1021/acs.jproteome.4c00688
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Panda, P., Ferreira, C. R., Cooper, B. R., Schaser, A. J., & Aryal, U. K. (2025). Multiplatform Lipid Analysis of the Brain of Aging Mice by Mass Spectrometry. Journal of Proteome Research. https://doi.org/10.1021/acs.jproteome.4c00688